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Embryonic differentiation is the process of development during which embryonic cells specialize and diverse tissue structures arise. Animals are made up of many different cell types, each with specific functions in the body. However, during early embryonic development, the embryo does not yet possess these varied cells; this is where embryonic differentiation comes into play. The differentiation of cells during embryogenesis is the key to cell, tissue, organ, and organism identity.

In 1947, Carl Richard Moore, a researcher at the University of Chicago, in Chicago, Illinois, wrote Embryonic Sex Differentiation and Sex Hormones, which was published in the same year as a first-edition monograph. In the book, Moore argues that regulation of sex differentiation in mammals is not controlled by sex hormones secreted by embryonic sex organs (gonads), but is controlled by non-hormonal genetic factors.

In 1974, Elizabeth Dexter Hay and Stephen Meier in the US conducted an experiment that demonstrated that the extracellular matrix, the mesh-like network of proteins and carbohydrates found outside of cells in the body, interacted with cells and affected their behaviors. In the experiment, Hay and Meier removed the outermost layer of cells that line the front of the eye, called corneal epithelium, from developing chick embryos.

In this paper Viktor Hamburger and Rita Levi-Montalcini collaborated to examine the effects of limb transplantation and explantation on neural development. In 1947 Hamburger invited Levi-Montalcini to his lab at Washington University in St. Louis to examine this question. Independently, each had previously arrived at opposing conclusions based on the same data.

Paul M. Brakefield and his research team in Leiden, the Netherlands, examined the development, plasticity, and evolution of butterfly eyespot patterns, and published their findings in Nature in 1996. Eyespots are eye-shaped color patterns that appear on the wings of some butterflies and birds as well as on the skin of some fish and reptiles. In butterflies, such as the peacock butterfly Aglais, the eyespots resemble the eyes of birds and help butterflies deter potential predators.

Carl Richard Moore was a professor and researcher at the University of Chicago in Chicago, Illinois who studied sex hormones in animals from 1916 until his death in 1955. Moore focused on the role of hormones on sex differentiation in offspring, the optimal conditions for sperm production, and the effects of vasectomy or testicular implants on male sex hormone production. Moore's experiments to create hermaphrodites in the laboratory contributed to the theory of a feedback loop between the pituitary and fetal gonadal hormones to control sex differentiation.

Roy John Britten studied DNA sequences in the US in the second
half of the twentieth century, and he helped discover repetitive
elements in DNA sequences. Additionally, Britten helped propose
models and concepts of gene regulatory networks. Britten studied the
organization of repetitive elements and, analyzing data from the
Human Genome Project, he found that the repetitive elements in DNA
segments do not code for proteins, enzymes, or cellular parts.
Britten hypothesized that repetitive elements helped cause cells to

Research in chemical induction seeks to identify the compound or compounds responsible for differentiation in a developing embryo. Soren Lovtrup compared the search for these compounds to the search for the philosopher's stone. It was based on the assumption that the differentiating agents have to be chemical substances either within cells or in the extracellular matrix.

Among other functions, the Notch signaling pathway forestalls the process of myogenesis in animals. The Notch signaling pathway is a pathway in animals by which two adjacent cells within an organism use a protein named Notch to mechanically interact with each other. Myogenesis is the formation of muscle that occurs throughout an animal's development, from embryo to the end of life. The cellular precursors of skeletal muscle originate in somites that form along the dorsal side of the organism.

The Notch signaling pathway is a mechanism in animals by which adjacent cells communicate with each other, conveying spatial information and genetic instructions for the animal's development. All multicellular animals utilize Notch signaling, which contributes to the formation, growth, and development of embryos (embryogenesis). Notch signaling also contributes to the differentiation of embryonic cells into various types of cells into various types of cells, such as neurons.

Conrad Hal Waddington's Organisers and Genes, published in 1940, is a summary of available research and theoretical framework for many concepts related to tissue differentiation in the developing embryo. The book is composed of two main conceptual sections. The first section explores the action and nature of the organizer, while the second section delves into genes and their influence on development.

The term morphogenesis generally refers to the processes by which order is created in the developing organism. This order is achieved as differentiated cells carefully organize into tissues, organs, organ systems, and ultimately the organism as a whole. Questions centered on morphogenesis have aimed to uncover the mechanisms responsible for this organization, and developmental biology textbooks have identified morphogenesis as one of the main challenges in the field. The concept of morphogenesis is intertwined with those of differentiation, growth, and reproduction.

The source-sink model, first proposed by biologist Francis Crick in 1970, is a theoretical system for how morphogens distribute themselves across small fields of early embryonic cells. A morphogen is a substance that determines the fate and phenotype of a group of cells through a concentration gradient of itself across that group. Crick’s theory has been experimentally confirmed with several morphogens, most notably with the protein bicoid , the first discovered morphogen. The model provides a theoretical structure for the understanding of some features of early embryonic development.

Charles Manning Child designed an experimental test, the susceptibility assay, to measure the effects of different toxins on developmental processes. The susceptibility assay measured an organism s vulnerability to death when it was submerged in a noxious solution. The assay involved immersing an organism in a solution that contained a depressant or inhibitory substance, such as alcohol, and then measuring the responses of the organism. Child interpreted these measurements as revealing information about the relative levels of metabolic activity within the organism.

Hilde Mangold, previously Hilde Proescholdt, was a German embryologist and physiologist who became well known for research completed with Hans Spemann in the 1920s. As a graduate student, Mangold assisted Spemann and together they discovered and coined the term the "organizer." The organizer discovery was a crucial contribution to embryology that led to further understanding of the pattern of embryo differentiation of amphibians.

"Induction and Patterning of the Primitive Streak, an Organizing Center of Gastrulation in the Amniote," (hereafter referred to as "Induction") examines the mechanisms underlying early amniote gastrulation and the formation of the primitive streak and midline axis. The review, authored by Takashi Mikawa and colleagues at Cornell University Medical College, was published in Developmental Dynamics in 2004.

Stem cells are undifferentiated cells that are capable of dividing for long periods of time and can give rise to specialized cells under particular conditions. Embryonic stem cells are a particular type of stem cell derived from embryos. According to US National Institutes of Health (NIH), in humans, the term "embryo" applies to a fertilized egg from the beginning of division up to the end of the eighth week of gestation, when the embryo becomes a fetus. Between fertilization and the eighth week of gestation, the embryo undergoes multiple cell divisions.

Between February 1969 and August 1970 Edward Kollar and Grace Baird, from the University of Chicago in Chicago, Illinois, published three papers that established the role of the mesenchyme in tooth induction. Drawing upon a history of using tissue interactions to understand differentiation, Kollar and Baird designed their experiments to understand how differentiated structures become specified. Their work overturned a widely accepted model that epithelium controls the identity of the structure, a phenomenon called structural specificity.

In 1962 researcher John Bertrand Gurdon at the University of Oxford in Oxford, England, conducted a series of experiments on the developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. In the experiments, Gurdon conducted nuclear transplantation, or cloning, of differentiated cells, or cells that have already specialized to become one cell type or another, in tadpoles. Gurdon's experiment showed that differentiated adult cells could be induced to an undifferentiated state, where they could once again become multiple cell types.

In 1952 Robert Briggs and Thomas J. King published their article, "Transplantation of Living Nuclei from Blastula Cells into Enucleated Frogs' Eggs," in the Proceedings of the National Academy of Sciences, the culmination of a series of experiments conducted at the Institute for Cancer Research and Lankenau Hospital Research Institute in Philadelphia, Pennsylvania. In this paper Briggs and King examined whether nuclei of embryonic cells are differentiated, and by doing so, were the first to conduct a successful nuclear transplantation with amphibian embryos.

The hedgehog signaling pathway is a mechanism that regulates cell growth and differentiation during embryonic development, called embryogenesis, in animals. The hedgehog signaling pathway works both between cells and within individual cells.

The epigenetic landscape is a concept representing embryonic development. It was proposed by Conrad Hal Waddington to illustrate the various developmental pathways a cell might take toward differentiation. The epigenetic landscape integrates the connected concepts of competence, induction, and regulative abilities of the genes into a single model designed to explain cellular differentiation, a long standing problem in embryology.

In 1969, Roy J. Britten and Eric H. Davidson published Gene Regulation for Higher Cells: A Theory, in Science. A Theory proposes a minimal model of gene regulation, in which various types of genes interact to control the differentiation of cells through differential gene expression. Britten worked at the Carnegie Institute of Washington in Washington, D.C., while Davidson worked at the California Institute of Technology in Pasadena, California. Their paper was an early theoretical and mechanistic description of gene regulation in higher organisms.

Conrad Hal Waddington's "Experiments on Embryonic Induction III," published in 1934 in the Journal of Experimental Biology, describes the discovery that the primitive streak induces the mammalian embryo. Waddington's hypothesis was that a transplanted primitive streak could induce neural tissue in the ectoderm of the rabbit embryo. The primitive streak defines the axis of an embryo and is capable of inducing the differentiation of various tissues in a developing embryo during gastrulation.

As mice embryos develop, they undergo a stage of development called gastrulation. The hallmark of vertebrate gastrulation is the reorganization of the inner cell mass (ICM) into the three germ layers: ectoderm, mesoderm, and endoderm. Mammalian embryogenesis occurs within organisms; therefore, gastrulation was originally described in species with easily observable embryos. For example, the African clawed frog (Xenopus laevis) is the most widely used organism to study gastrulation because the large embryos develop inside a translucent membrane.